The goal of this project is to develop improved drug therapies for nervious system disease. Clinical and preclinical investigations seek to elucidate how the activity of specific transmitter systems relate to neuropsychiatric function. Based on these relationships, novel pharmaceutical agents are evaluated for their ability to influence central synaptic processes and thus modify neurologic symptoms. Major topics now under study include: 1) Application of the oxygen-18 technique to evaluate central monoaminergic mechanisms and the fluorodeoxyglucose method combined with positron emission tomography to assess regional neuronal function in man. 2) Relation of the dopamine system and of closely interactive transmitter systems to extrapyramidal motor function. 3) Ability of selected agonists and antagonists of dopamine, gamma aminobutyric acid, and certain peptides to influence motor and cognitive behavior.